Abstract

Stochastic Events in Cell signalling The set of biochemical reactions by which an E. coli bacterium detects and responds to distant sources of attractant or repellent molecules is probably the simplest and best understood example of a cell signalling pathway. The pathway has been saturated genetically and all of its protein components have been isolated, measured biochemically, and their atomic structures determined. We are using detailed computer simulations, tied to experimental data, to ask how the pathway works as an integrated unit. Increasingly we find that the physical location of molecular components within the molecular jungle of the cell interior is crucial for an understanding of their function. Allosteric interactions between protein molecules appear to be important for the switching characteristics of the flagellar motor, and the high amplification of signals at the chemotactic receptors.

A suite of algorithms (called Smoldyn – for Smoluchowski Dynamics) was developed by Steven Andrews to track the diffusive trajectory and chemical reactions of individual molecules in three dimensions. Karen Lipkow is now using this program to explore the movements of CheY – the only freely diffusing protein in the bacterial chemotaxis pathway – through the bacterial cytoplasm. We are addressing such questions as how quickly CheY diffuses from the receptors to the flagellar motors? What gradients of CheY are be set up and how will they depend on external stimuli? We are particularly interested in the issue of molecular crowding and how this will affect diffusion in the cytoplasm and hence the bacterial response.

For more information please see: http://www.pdn.cam.ac.uk/comp-cell